K+ currents play a major role in membrane excitability. Repolarizing outward currents are carried out almost exclusively by K+ channel conductances and/or distributions of K+ channels may be modulated in order to generate excitable membrane diversity. Although much is known about K+ channel physiology and pharmacology, relatively little is known about its molecular basis. The present research uses electrophysiological and molecular genetic methods to examine K+ channels. The goal is to provide a molecular understanding of K+ channel structure and function. Experiments focus on the Shaker (Sh) gene complex in Drosophila that encodes K+ channels. We have previously cloned the chromosomal region containing Sh. In the present proposal we will continue to use molecular genetic methodologies to identify the DNA sequences which encode Sh. We will use nucleotide sequence methods to deduce the amino acid sequence of the channel encoded by Sh. Finally, we will examine methods that may be used to identify other K+ channel genes in Drosophila. Sh is one of the best-studied sets of nervous system genes. Physiological, genetic, and molecular genetic analyses of Sh provide basic research with important implication for any nervous system disease with a heritable component.